Herpes zoster is a common and painful neurological disease that is caused by reactivation of the varicella-zoster virus. Herpes zoster pain that persists after healing of the acute infection is termed postherpetic neuralgia (PHN), a chronic pain syndrome that is often refractory to all treatment. The prevalence of PHN is expected to increase substantially in the coming decades because the incidence of herpes zoster and the risk of PHN will both increase as the population ages. Although research to improve treatment is continuing, as many as half of all patients do not currently obtain relief. For this reason, the development of interventions that prevent PHN would lead to major reductions in disability, distress, and use of health care resources. On the basis of the results of research on risk factors for PHN and its pathophysiologic mechanisms, it can be hypothesized that combined antiviral and analgesic treatment begun as soon as possible after the -onset of herpes zoster will reduce the risk of PHN. The specific aim of this planning grant is to develop the protocol and procedures for a clinical trial to test this hypothesis. The proposed trial will have the following major objectives: The primary aim will be to test the hypothesis that the risk of PHN is reduced by half in herpes zoster patients treated with an antiviral agent and an opioid analgesic compared with patients treated with the antiviral agent and matching placebo. Support for this hypothesis would have a major impact on the treatment of patients with herpes zoster and lead to a substantial reduction in the prevalence of PHN. A second major aim that will be accomplished by the proposed trial is determining whether the initiation of central mechanisms of chronic neuropathic pain can be prevented by attenuating acute pain. The answer to this question will provide important information about mechanisms of prolonged pain and have major implications for its prevention.